Previous studies suggest that the osteoprotegerin gene (OPG) plays an important role in the development of osteoporosis. This study aims to investigate the potential association between OPG genetic polymorphisms and bone mineral density (BMD) and osteoporosis in postmenopausal women. 938 Chinese postmenopausal women were enrolled. The lumbar spine (L(2-4)) BMD, neck BMD, and total hip BMD were measured by dual energy X-ray absorptiometry (DEXA). The genotypes of OPG genetic polymorphisms were evaluated by the created restriction site-polymerase chain reaction (CRS-PCR), PCR-restriction fragment length polymorphism (PCR-RFLP), and DNA sequencing methods. Our data indicated that subjects with genotype TT of the g.26395T>C genetic polymorphism showed a significantly higher adjusted value of BMD when compared with those of genotypes TC and CC. Subjects with genotype AA of the g.27649A>G genetic polymorphism showed a significantly higher adjusted value of BMD than those of genotypes AG and GG. These findings suggest that the OPG genetic polymorphisms may affect BMD and osteoporosis in Chinese postmenopausal women.